Sandbox Reserved 1600: Difference between revisions

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The ''Geobacillus thermodenitrificans'' organism utilizes the bd oxidase mechanism. The oxygen enters the enzyme through the selective <scene name='83/832926/Potential_oxygen_entry_site/1'>oxygen entry site</scene> that funnels the extracellular oxygen to <scene name='83/838655/Bd_oxidase_heme_d/1'>Heme D</scene> in the active site. The electrons for the reaction are provided ADD MORE SPECIFIC DESCRIPTION OF ELECTRONS TO ORGANISM. The protons for the reaction are provided by one of two <scene name='83/838655/Bdoxidase_proton_pathways/1'>potential proton pathways</scene>, either the <scene name='83/838655/Bdoxidase_cyda_pathway/6'>CydA pathway</scene>or <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>. Both of the proton pathways utilize the intracellular water molecules for the proton source, and shuttle them to <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene>.

= Biological Importance of Reducing O₂ =

Oxygen toxicity is a fatal problem among all organisms, but can easily occur in prokaryotes due to their low oxygen tolerance. In prokaryotes, the cytochrome Bd oxygen reductases function to quickly reduce the concentration of O2 into H2O to protect the cell from detrimental effects. Without proper functioning of these enzymes, or if O2 concentrations are too high, the concentrations of the intermediates formed from the reduction reaction will increase and can be detrimental. As a result of the vitality of reducing O2 in prokaryotes, knowledge on Bd oxidases can help develop drugs that target these enzymes to combat bacterial infection <ref name=”Borisov”>PMID:21756872</ref>.

=Structure=

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[[Image:Hemes2.png|300 px|right|thumb|Figure 1. The active site of bd oxidase for ''Geobacillus thermodenitrificans''. Heme B558 (pink; left), Heme B595 (pink; right), and Heme D (green). Important residues shown in blue. Measurements are shown in Å.]]

The active site for Bd Oxidase in ''Geobacillus thermodenitrificans'' is located in subunit Cyd A. The site consists of three iron hemes: <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene>, <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene>, and <scene name='83/838655/Bd_oxidase_heme_d/1'>Heme D</scene> that are held together in a rigid triangular <scene name='83/838655/Hemes/6'>arrangement</scene> due to Van der Waals interactions <ref name = ”Safarian” />. The <scene name='83/838655/Hemes_measurements/1'>length</scene> between each heme's central iron is relatively constant which serves to shuttle protons and electrons from one heme to another efficiently (Fig. 1). It is suggested that <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> acts as an electron acceptor, orientated toward the extracellular side by His186, Met325, Lys182, and Lys252 (Fig. 1) <ref name = ”Safarian” />. With <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> closest in proximity to the intracellular side, it is suggested it functions as the proton acceptor with two potential proton pathways. It is then proposed that both <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> and <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> shuttle their respective ions directly to <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> based on this being the shortest pathway. <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> is thus indicated to be the oxygen binding site due to proximity and orientation to the exterior surface of the protein <ref name = ”Safarian” />.

The active site for Bd Oxidase in ''Geobacillus thermodenitrificans'' is located in subunit Cyd A. The site consists of three iron hemes: <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene>, <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene>, and <scene name='83/838655/Bd_oxidase_heme_d/1'>Heme D</scene> that are held together in a rigid triangular <scene name='83/838655/Hemes/6'>arrangement</scene> due to Van der Waals interactions <ref name = ”Safarian” />. The <scene name='83/838655/Hemes_measurements/1'>length</scene> between each heme's central iron is relatively constant which serves to shuttle protons and electrons from one heme to another efficiently (Fig. 1). It is suggested that <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> acts as an electron acceptor, orientated toward the extracellular side by His186, Met325, Lys182, and Lys252 (Fig. 1) <ref name = ”Safarian” />. With <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> closest in proximity to the intracellular side, it is suggested it functions as the proton acceptor with two potential proton pathways. It is then proposed that both <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> and <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> shuttle their respective ions directly to <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> based on this being the shortest pathway.

==Potential Oxygen Entry Site==

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When all of these elements of the reduction aggregate in the active site, the protons and electrons are shuttled to Heme D, where the actual reduction occurs. The 2H₂O molecules are then expelled, as seen in red in Figure 4. The shuttling of these electrons and protons also helps assist with the electric chemical potential in the cellular membrane.

~~= Biological Importance of Reducing O₂ =~~

= Structure Similarity to bd oxidase found in ''E. coli'' =

[[Image:Aligmentbdoidase.jpg|200 px|left|thumb|Figure 5. Alignment of bd oxidase for the organisms ''Geobacillus thermodenitrificans'' (blue) and ''E. coli'' (purple).]] [[Image:Heme alignment.png|200 px|right|thumb|Figure 6. Heme arrangements for the organisms ''Geobacillus thermodenitrificans'' and ''E. coli''. Heme D (green); Heme B595 and Heme B558 shown in pink]] The structure of bd oxidase for ''Geobacillus thermodenitrificans'' is highly similar to the structure of bd oxidase for [[6rko|''E. coli'']] with the only noticeable difference being the length of the Q-loop. <ref name= ”Theßeling”>PMID:31723136</ref> The similarity and differences between the two proteins can be seen in the alignment of their main structures (Fig.5). Although only having one noticeable difference in structure, this difference causes the two proteins to have different active sites (Fig. 6). In particular, the <scene name='83/838655/Hemes_ecoli/2'>hemes of bd oxidase in ''E. coli'' </scene> are arranged differently than the <scene name='83/838655/Hemes/4'>hemes in ''Geobacillus thermodenitrificans''</scene>. The main reason for this change in heme arrangement is because of the <scene name='83/838655/Oxygen_site_ecoli/1'>oxygen binding site</scene> being located differently in ''E. coli'', thus causing a different active site arrangement in the protein <ref name = ”Theßeling” />. ~~For~~

[[Image:Aligmentbdoidase.jpg|200 px|left|thumb|Figure 5. Alignment of bd oxidase for the organisms ''Geobacillus thermodenitrificans'' ([[PBD: 5DOQ]]) shown in blue and ''E. coli'' ([[PBD: 6RKO]]) shown in purple.]] [[Image:Heme alignment.png|200 px|right|thumb|Figure 6. Heme arrangements for the organisms ''Geobacillus thermodenitrificans'' and ''E. coli''. Heme D (green); Heme B595 and Heme B558 shown in pink]] The structure of bd oxidase for ''Geobacillus thermodenitrificans'' is highly similar to the structure of bd oxidase for [[6rko|''E. coli'']] with the only noticeable difference being the length of the Q-loop. <ref name= ”Theßeling”>PMID:31723136</ref> The similarity and differences between the two proteins can be seen in the alignment of their main structures (Fig.5). Although only having one noticeable difference in structure, this difference causes the two proteins to have different active sites (Fig. 6). In particular, the <scene name='83/838655/Hemes_ecoli/2'>hemes of bd oxidase in ''E. coli'' </scene> are arranged differently than the <scene name='83/838655/Hemes/4'>hemes in ''Geobacillus thermodenitrificans''</scene>. The main reason for this change in heme arrangement is because of the <scene name='83/838655/Oxygen_site_ecoli/1'>oxygen binding site</scene> being located differently in ''E. coli'', thus causing a different active site arrangement in the protein <ref name = ”Theßeling” />.

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@@ Line 13: / Line 13: @@
 The ''Geobacillus thermodenitrificans'' organism utilizes the bd oxidase mechanism. The oxygen enters the enzyme through the selective <scene name='83/832926/Potential_oxygen_entry_site/1'>oxygen entry site</scene> that funnels the extracellular oxygen to <scene name='83/838655/Bd_oxidase_heme_d/1'>Heme D</scene> in the active site. The electrons for the reaction are provided ADD MORE SPECIFIC DESCRIPTION OF ELECTRONS TO ORGANISM. The protons for the reaction are provided by one of two <scene name='83/838655/Bdoxidase_proton_pathways/1'>potential proton pathways</scene>, either the <scene name='83/838655/Bdoxidase_cyda_pathway/6'>CydA pathway</scene>or <scene name='83/838655/Bdoxidase_cydb_pathway/3'>CydB pathway</scene>. Both of the proton pathways utilize the intracellular water molecules for the proton source, and shuttle them to <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene>.
+= Biological Importance of Reducing O₂ =
+Oxygen toxicity is a fatal problem among all organisms, but can easily occur in prokaryotes due to their low oxygen tolerance. In prokaryotes, the cytochrome Bd oxygen reductases function to quickly reduce the concentration of O2 into H2O to protect the cell from detrimental effects. Without proper functioning of these enzymes, or if O2 concentrations are too high, the concentrations of the intermediates formed from the reduction reaction will increase and can be detrimental. As a result of the vitality of reducing O2 in prokaryotes, knowledge on Bd oxidases can help develop drugs that target these enzymes to combat bacterial infection <ref name=”Borisov”>PMID:21756872</ref>.
 =Structure=
@@ Line 23: / Line 27: @@
 [[Image:Hemes2.png|300 px|right|thumb|Figure 1. The active site of bd oxidase for ''Geobacillus thermodenitrificans''. Heme B558 (pink; left), Heme B595 (pink; right), and Heme D (green). Important residues shown in blue. Measurements are shown in Å.]]
-The active site for Bd Oxidase in ''Geobacillus thermodenitrificans'' is located in subunit Cyd A. The site consists of three iron hemes: <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene>, <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene>, and <scene name='83/838655/Bd_oxidase_heme_d/1'>Heme D</scene> that are held together in a rigid triangular <scene name='83/838655/Hemes/6'>arrangement</scene> due to Van der Waals interactions <ref name = ”Safarian” />. The <scene name='83/838655/Hemes_measurements/1'>length</scene> between each heme's central iron is relatively constant which serves to shuttle protons and electrons from one heme to another efficiently (Fig. 1). It is suggested that <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> acts as an electron acceptor, orientated toward the extracellular side by His186, Met325, Lys182, and Lys252 (Fig. 1) <ref name = ”Safarian” />. With <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> closest in proximity to the intracellular side, it is suggested it functions as the proton acceptor with two potential proton pathways. It is then proposed that both <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> and <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> shuttle their respective ions directly to <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> based on this being the shortest pathway. <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> is thus indicated to be the oxygen binding site due to proximity and orientation to the exterior surface of the protein <ref name = ”Safarian” />.
+The active site for Bd Oxidase in ''Geobacillus thermodenitrificans'' is located in subunit Cyd A. The site consists of three iron hemes: <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene>, <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene>, and <scene name='83/838655/Bd_oxidase_heme_d/1'>Heme D</scene> that are held together in a rigid triangular <scene name='83/838655/Hemes/6'>arrangement</scene> due to Van der Waals interactions <ref name = ”Safarian” />. The <scene name='83/838655/Hemes_measurements/1'>length</scene> between each heme's central iron is relatively constant which serves to shuttle protons and electrons from one heme to another efficiently (Fig. 1). It is suggested that <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> acts as an electron acceptor, orientated toward the extracellular side by His186, Met325, Lys182, and Lys252 (Fig. 1) <ref name = ”Safarian” />. With <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> closest in proximity to the intracellular side, it is suggested it functions as the proton acceptor with two potential proton pathways. It is then proposed that both <scene name='83/838655/Bd_oxidase_heme_558/2'>Heme B558</scene> and <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> shuttle their respective ions directly to <scene name='83/838655/Bd_oxidase_heme_b_595/1'>Heme B595</scene> based on this being the shortest pathway.
 ==Potential Oxygen Entry Site==
@@ Line 50: / Line 54: @@
 When all of these elements of the reduction aggregate in the active site, the protons and electrons are shuttled to Heme D, where the actual reduction occurs. The 2H₂O molecules are then expelled, as seen in <font color='red'><b>red</b></font> in Figure 4. The shuttling of these electrons and protons also helps assist with the electric chemical potential in the cellular membrane.
-= Biological Importance of Reducing O₂ =
 = Structure Similarity to bd oxidase found in ''E. coli'' =
-[[Image:Aligmentbdoidase.jpg|200 px|left|thumb|Figure 5. Alignment of bd oxidase for the organisms ''Geobacillus thermodenitrificans'' (blue) and ''E. coli'' (purple).]] [[Image:Heme alignment.png|200 px|right|thumb|Figure 6. Heme arrangements for the organisms ''Geobacillus thermodenitrificans'' and ''E. coli''. Heme D (green); Heme B595 and Heme B558 shown in pink]] The structure of bd oxidase for ''Geobacillus thermodenitrificans'' is highly similar to the structure of bd oxidase for [[6rko|''E. coli'']] with the only noticeable difference being the length of the Q-loop. <ref name= ”Theßeling”>PMID:31723136</ref> The similarity and differences between the two proteins can be seen in the alignment of their main structures (Fig.5).  Although only having one noticeable difference in structure, this difference causes the two proteins to have different active sites (Fig. 6). In particular, the <scene name='83/838655/Hemes_ecoli/2'>hemes of bd oxidase in ''E. coli'' </scene> are arranged differently than the <scene name='83/838655/Hemes/4'>hemes in ''Geobacillus thermodenitrificans''</scene>. The main reason for this change in heme arrangement is because of the  <scene name='83/838655/Oxygen_site_ecoli/1'>oxygen binding site</scene> being located differently in ''E. coli'', thus causing a different active site arrangement in the protein <ref name = ”Theßeling” />. For
+[[Image:Aligmentbdoidase.jpg|200 px|left|thumb|Figure 5. Alignment of bd oxidase for the organisms ''Geobacillus thermodenitrificans'' ([[PBD: 5DOQ]]) shown in <font color='blue'><b>blue</b></font> and ''E. coli'' ([[PBD: 6RKO]]) shown in <font color='purple'><b>purple</b></font>.]] [[Image:Heme alignment.png|200 px|right|thumb|Figure 6. Heme arrangements for the organisms ''Geobacillus thermodenitrificans'' and ''E. coli''. Heme D (green); Heme B595 and Heme B558 shown in pink]] The structure of bd oxidase for ''Geobacillus thermodenitrificans'' is highly similar to the structure of bd oxidase for [[6rko|''E. coli'']] with the only noticeable difference being the length of the Q-loop. <ref name= ”Theßeling”>PMID:31723136</ref> The similarity and differences between the two proteins can be seen in the alignment of their main structures (Fig.5).  Although only having one noticeable difference in structure, this difference causes the two proteins to have different active sites (Fig. 6). In particular, the <scene name='83/838655/Hemes_ecoli/2'>hemes of bd oxidase in ''E. coli'' </scene> are arranged differently than the <scene name='83/838655/Hemes/4'>hemes in ''Geobacillus thermodenitrificans''</scene>. The main reason for this change in heme arrangement is because of the  <scene name='83/838655/Oxygen_site_ecoli/1'>oxygen binding site</scene> being located differently in ''E. coli'', thus causing a different active site arrangement in the protein <ref name = ”Theßeling” />.